The Influence of Preimplant Balancing on Manipulation under Anesthesia Rates following Imageless Robotic-Assisted Total Knee Arthroplasty.

Acquired idiopathic stiffness (AIS) following total knee arthroplasty (TKA) often requires manipulation under anesthesia (MUA). Robotic-assisted TKA (RA-TKA) systems provide gap balance templates for objective correlation with the rate of AIS. The purpose of this study was to assess intraoperative balancing parameters that were associated with MUA utilizing an "anatomical" implant design.We performed a retrospective chart review of 265 imageless RA-TKA procedures performed by R.M. and K.D. between 2018 and 2020. The primary outcome for AIS or clinically significant "arthrofibrosis" was MUA. Patient intraoperative gap planning data were examined for association.The rate of MUA was 8.7% (23/265), which was performed at a mean follow-up time of 75.9 ± 32.2 days. The lateral to medial gap difference in extension was significantly less in patients requiring MUA (odds ratio [OR] = 0.86, 95% confidence interval [CI], 0.75-0.99) (p = 0.034). Significantly less preoperative varus mechanical axis was associated with knees requiring MUA (1.83° vs. 4.04°, OR = 1.09, 95% CI, 1.00-1.19). Decreased templated mechanical axis correction was associated with MUA (2.09° vs. 4.75°, p < 0.0001).A tighter lateral-to-medial gap in extension, less preoperative varus, and smaller templated mechanical axis corrections were associated with increased rates of MUA.

CNS Embryonal Tumor with PLAGL Amplification, a New Tumor Type in Children and Adolescents: Insights from a Comprehensive MRI Analysis.

BACKGROUND AND PURPOSE: CNS embryonal tumor with PLAGL1/PLAGL2 amplification (ET, PLAGL) is a newly identified, highly malignant pediatric tumor. Systematic MRI descriptions of ET, PLAGL are currently lacking. MATERIALS AND METHODS: MRI data from 19 treatment-naïve patients with confirmed ET, PLAGL were analyzed. Evaluation focused on anatomical involvement, tumor localization, MRI signal characteristics, DWI behavior, and the presence of necrosis and hemorrhage. Descriptive statistics (median, interquartile range, percentage) were assessed. RESULTS: Ten patients had PLAGL1 and nine PLAGL2 amplifications. The solid components of the tumors were often multinodular with heterogeneous enhancement (mild to intermediate in 47% and intermediate to strong in 47% of cases). Non-solid components included cysts in 47% and necrosis in 84% of the cases. The tumors showed heterogeneous T2WI hyper-and isointensity (74%), relatively little diffusion restriction (ADC values < contralateral normal-appearing WM in 36% of cases with available DWI), and tendencies towards hemorrhage/calcification (42%). No reliable distinction was found between PLAGL1-and PLAGL2-amplified tumors or compared to other embryonal CNS tumors. CONCLUSIONS: The study contributes to understanding the imaging characteristics of ET, PLAGL. It underscores the need for collaboration in studying rare pediatric tumors and advocates for the use of harmonized imaging protocols for better characterization. ABBREVIATIONS: ATRT= atypical teratoid/rhabdoid tumor; ETMR= embryonal tumor with multilayered rosettes; ET, PLAGL= CNS embryonal tumor with PLAGL amplification; EVD= external ventricular drain; IQR: interquartile range; PLAGL1= pleomorphic adenoma gene-like 1; PLAGL2= pleomorphic adenoma gene-like 2; WHO= World Health Organization.

Evaluation of a host-protein signature score for differentiating between bacterial and viral infections: real-life evidence from a German tertiary hospital.

PURPOSE: A host-protein signature score, consisting of serum-concentrations of C-reactive protein, tumour necrosis factor-related apoptosis-inducing ligand, and interferon gamma-induced protein 10, was validated for distinguishing between bacterial and viral infections as an antimicrobial stewardship measure for routine clinical practice among adult patients in a German tertiary hospital. METHODS: This single-centre, explorative study prospectively assessed the host-protein signature score, comparing it with serum procalcitonin (PCT) in patients with blood stream infections (BSI) and evaluating its efficacy in patients with viral infections against the standard of care (SOC) to assess the need for antibiotics due to suspected bacterial super/coinfection. Manufacturer-specified threshold scores were used to differentiate viral (< 35) and bacterial (> 65) infections. RESULTS: Ninety-seven patients (BSI [n = 56]; viral infections [n = 41]) were included. The score (cut-off score > 65) tended to detect BSI with higher sensitivity than did PCT (cut-off > 0.5 ng/mL) (87.5% vs. 76.6%). Three patients (5.4%) with BSI had a score < 35. One patient with BSI did not receive antibiotic treatment following SOC prior to positive blood culture results. Among patients with viral infections, 29 (70.7%) had scores > 65, indicating bacterial superinfections. Additionally, 11 patients (26.8%) had scores < 35, indicating no bacterial superinfections. In total, the antibiotic treatment discrepancy in the viral group between the SOC and a host-protein signature score guided approach was 2/41 patients (4.9%). CONCLUSION: The score tended towards a higher sensitivity in detecting BSI than that with PCT. However, its impact on reducing antibiotic use in viral infections was minor compared with that of SOC.

Evaluation of postoperative peri-implant reactive tissues following implant supported prosthetic rehabilitation in fibula free flaps.

OBJECTIVES: The purpose of this study was to measure the frequency of peri-implant reactive tissue development in a cohort of patients following immediate implant supported prosthetic rehabilitation in fibula free flaps at our institution and to document 2 cases of management based on our institution's experience. STUDY DESIGN: To address this question of study design, a case series was performed from October 2014 to May 2022. We included patients that underwent a fibula free flap reconstruction of the mandible or maxilla with immediate implant placement and dental prostheses fabrication. Forty-four patients met the inclusion criteria, and, among the participants, a total of 26 male patients (59%) and 18 female patients (41%) were evaluated, with 185 implants placed all together. RESULTS: Twenty patients (45%) were treated for benign pathology, 12 with malignant pathology (27%), 5 with trauma (11%), and 7 with osteoradionecrosis (16%). Postoperative peri-implant reactive tissues were seen to develop at 39 of the implant sites (21%). CONCLUSION: Reactive tissues were found to be a common complication in patients treated with fibular free flap reconstructions involving implant rehabilitation. Our institution noted that local excision of such reactive tissues, in addition to silver nitrate cauterization and topical steroid application, may provide reasonable success in dealing with these occurrences. (Oral Surg Oral Med Oral Pathol Oral Radiol YEAR;VOL:page range).

Ultrasonographic liver nodules are more often benign lesions in dogs with hemoperitoneum secondary to splenic tumor rupture.

OBJECTIVE: To evaluate the reliability of preoperative abdominal ultrasonography as a staging tool for dogs with hemoperitoneum due to presumed splenic tumor rupture, focusing on the detection of metastatic lesions in the liver. ANIMALS: 99 dogs from 20 emergency and specialty hospitals across the US. METHODS: Dogs with nontraumatic hemoperitoneum secondary to splenic tumor rupture were included. A post hoc analysis was conducted on data from a nationwide prospective trial investigating novel treatments for canine hemangiosarcoma. The accuracy of preoperative staging was assessed by comparing ultrasonographic findings with intraoperative observations and histologic findings. RESULTS: On preoperative ultrasonography, there was a 20% incidence of liver lesions identified, with no association to liver lesions seen during operation. Notably, 22% of liver lesions observed during operation were missed on preoperative ultrasonography. The presence of liver lesions on preoperative ultrasonography was associated with a higher likelihood of a benign splenic tumor diagnosis. There was no association between the identification of liver lesions on preoperative ultrasonography and the presence of metastatic disease on liver biopsy, with a sensitivity and specificity of 19% and 82%, respectively. Additionally, ultrasound had low sensitivity in detecting intra-abdominal lesions beyond the liver and spleen, with 82% of these lesions missed preoperatively. CLINICAL RELEVANCE: This study challenges conventional perceptions around the approach to staging in dogs with hemoperitoneum. These findings advocate for a reevaluation of the staging approach, with more comprehensive modalities like whole-body CT or MRI potentially being more warranted.

Middle meningeal artery embolization following surgical evacuation of symptomatic chronic subdural hematoma improves outcomes, interim results of a prospective randomized trial.

BACKGROUND: Outcomes after surgical treatment of chronic subdural hematoma (cSDH) remain undesirable in a significant proportion of patients. We aimed to show the role of middle meningeal artery (MMA) embolization and to demonstrate its benefits. METHODS: Thirty-five patients with symptomatic cSDH were enrolled in a prospective randomized trial following evacuation surgery. Participants were randomized to embolization or control group (expectant management following surgical evacuation without embolization). Patients were followed throughout their hospitalization and outpatient follow-ups. The main goals of this planned interim analysis were to assess neurological outcome and resource utilization. RESULTS: The groups were comparable in terms of sex, age and follow-up retention rates. Side(s) of intervention(s) and hematoma size were similar. There was no statistical difference in neurological examination improvement at discharge, but at follow-up, we observed a decline in neurologic exam in the control group (p = 0.03). Control group participants required more re-interventions (p = 0.02) and were followed in clinic and during related readmissions for longer (p = 0.02). The number of imaging studies obtained in relation to the disease management was higher in the control group (p = 0.01). CONCLUSIONS: Our results suggest a beneficial role for the addition of MMA embolization to surgical intervention in the treatment of symptomatic chronic subdural hematoma. Neurological outcomes were significantly better in the embolization group. This contributed to less need for follow-up, re-interventions, and imaging studies.

Tixagevimab/Cilgavimab for COVID-19 Pre-Exposure Prophylaxis in Hematologic Patients-A Tailored Approach Based on SARS-CoV-2 Vaccine Response.

Patients with hematologic malignancies still face a significant risk of severe coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-neutralizing monoclonal antibody combination tixagevimab/cilgavimab (TIX/CGB) could be administered to immunocompromised patients for pre-exposure prophylaxis (PrEP) before the emergence of TIX/CGB-resistant COVID-19 Omicron variants. TIX/CGB application could be carried out regardless of the host's immune response to previous active SARS-CoV-2 vaccinations or infections. Because the efficacy of COVID-19 PrEP remains unclear, especially in SARS-CoV-2-seropositive patients, German national guidelines recommended TIX/CGB PrEP only for SARS-CoV-2-seronegative patients in addition to an intensified active vaccination schedule. Having followed these guidelines, we now report the characteristics and outcomes of 54 recipients of TIX/CGB PrEP in SARS-CoV-2-seronegative patients with hematological disease from a German tertiary medical center and compare them to 125 seropositive patients who did not receive any PrEP. While the number of patients with B-cell lymphomas was significantly higher in the seronegative cohort (33 (61%) vs. 18 (14%) cases, p < 0.01), patients with myeloid diseases were significantly more frequent in the seropositive cohort (51 (41%) vs. 5 (9%) cases, p < 0.01). Strikingly, patients who had undergone allogeneic hematopoietic stem cell transplantation were significantly more likely (forty-nine (39%) vs. six (11%) cases, p < 0.01) to be SARS-CoV-2 seropositive. We observed that prophylactic application of TIX/CGB PrEP to a highly vulnerable group of SARS-CoV-2-seronegative patients resulted in a similar number of COVID-19 breakthrough infections compared to the untreated seropositive control group (16 (32%) vs. 39 (36%), p = 0.62) and comparable COVID-19-related outcomes like hospitalization and oxygen requirement throughout an extended follow-up period of 12 months. In conclusion, our results support the tailored approach of administering TIX/CGB PrEP only to SARS-CoV-2-seronegative patients during the COVID-19 pandemic and might provide a rationale for similar strategies during future outbreaks/diseases, especially in times of initial limited availability and/or financial constraints.

Benefits and Risks Associated With Antibiotic Prophylaxis for Thyroid Operations.

INTRODUCTION: Prophylactic antibiotics (pABX) are commonly used prior to thyroid operations despite clean case classification. The objective of this study was to assess the association of antibiotic prophylaxis with the incidence of surgical site infection (SSI) among patients undergoing thyroidectomy. METHODS: We performed a cohort study of all adults undergoing thyroid operations at a tertiary referral center from 2010 to 2019. The primary outcome was 30-d SSI, based on diagnosis codes and/or antibiotic use and further classified based on whether wound aspiration or operative washout were required. The association between pABX and SSI was determined using propensity score matching based on patient demographics and comorbidities likely to influence SSI risk. RESULTS: We identified 2411 patients who underwent thyroid operations, of whom 1358 (56.3%) received pABX. Patients who received pABX had a higher mean Charlson-Deyo Comorbidity Index score than patients who did not (3.6 versus 2.9). The unadjusted incidence of SSI was higher in patients who received pABX than those who did not (6.1% versus 3.4%, P < 0.001). Few patients with SSI required aspiration or operative washout (0.29% who received pABX versus 0.19% who did not). After propensity score matching, pABX use showed no association with overall 30-d SSI (odds ratio 1.38, 95% confidence interval 0.84-2.26) or SSI requiring procedural intervention (odds ratio 3.01, 95% confidence interval 0.24-158). CONCLUSIONS: In a large cohort of patients with a high prevalence of comorbidity, use of pABX was not associated with a decreased incidence of SSI following thyroid surgery. Efforts should be made to deimplement low-value pABX use in thyroid surgery.

Discovery of Pyrazolopyrazines as Selective, Potent, and Mutant-Active MET Inhibitors with Intracranial Efficacy.

Mesenchymal-epithelial transition factor (MET) is a receptor tyrosine kinase that serves a critical function in numerous developmental, morphogenic, and proliferative signaling pathways. If dysregulated, MET has been shown to be involved in the development and survival of several cancers, including non-small cell lung cancer (NSCLC), renal cancer, and other epithelial tumors. Currently, the clinical efficacy of FDA approved MET inhibitors is limited by on-target acquired resistance, dose-limiting toxicities, and less than optimal efficacy against brain metastasis. Therefore, there is still an unmet medical need for the development of MET inhibitors to address these issues. Herein we report the application of structure-based design for the discovery and development of a novel class of brain-penetrant MET inhibitors with enhanced activity against clinically relevant mutations and improved selectivity. Compound 13 with a MET D1228N cell line IC50 value of 23 nM showed good efficacy in an intracranial tumor model and increased the median overall survival of the animals to 100% when dosed orally at 100 mg/kg daily for 21 days.

Improved self-cleaving precipitation tags for efficient column free bioseparations.

Current biological research requires simple protein bioseparation methods capable of purifying target proteins in a single step with high yields and purities. Conventional affinity tag-based approaches require specific affinity resins and expensive proteolytic enzymes for tag removal. Purification strategies based on self-cleaving aggregating tags have been previously developed to address these problems. However, these methods often utilize C-terminal cleaving contiguous inteins which suffer from premature cleavage, resulting in significant product loss during protein expression. In this work, we evaluate two novel mutants of the Mtu RecA ΔI-CM mini-intein obtained through yeast surface display for improved protein purification. When used with the elastin-like-polypeptide (ELP) precipitation tag, the novel mutants - ΔI-12 and ΔI-29 resulted in significantly higher precursor content, product purity and process yield compared to the original Mtu RecA ΔI-CM mini-intein. Product purities ranging from 68 % to 94 % were obtained in a single step for three model proteins - green fluorescent protein (GFP), maltose binding protein (MBP) and beta-galactosidase (beta-gal). Further, high cleaving efficiency was achieved after 5 h under most conditions. Overall, we have developed improved self-cleaving precipitation tags which can be used for purifying a wide range of proteins cheaply at laboratory scale.